Tocilizumab for treatment of severe COVID morbidly obese patient with comorbidities

Ankita Aggarwal, Ishan Yadav, Mahima Lakhanpal
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Abstract

COVID-19, caused by the novel severe acute respiratory coronavirus 2, emerged in Wuhan, China, in 2019 and has resulted in the current pandemic. The disease continues to pose a major therapeutic challenge. Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS). Because interleukin-6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release. Tocilizumab is a recombinant humanized monoclonal antibody that serves as an IL-6 receptor inhibitor. Tocilizumab is beneficial for the treatment of inflammatory and autoimmune conditions and rheumatoid arthritis, giant cell arteritis, and systemic juvenile idiopathic arthritis. It is also under used in the treatment of severely ill patients with COVID-19. Patients with moderate-to-severe disease with progressively increasing oxygen requirements, with inadequate response to corticosteroids, and with raised levels of inflammatory markers (MoHFW, June 2020). It is used in dose of 8 mg/kg in 100 ml NS over 60 minutes (maximum dose 800 mg/infusion). It can be repeated once after 12 − 24 hours if needed. Careful monitoring for secondary infection and neutropenia should be done. It is contraindicated in people with HIV, active infections, tuberculosis, active hepatitis, ANC is <2000/mm3 and platelet count <100,000/mm3. We present the first case of our institution in which we administered tocilizumab, a 57-year-old female with moderate-to-severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress. The patient was treated with tocilizumab to prevent the cytokine storm. We chose early administration of an IL-6 inhibitor because of the gradually increasing levels of inflammatory markers and her deteriorating respiratory status. The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, tazar, and zinc). The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days. We believe that tocilizumab played a substantial role in her ability to overcome clinical decline, particularly the need for mechanical ventilation. Ultimately, the patient was shifted from the intensive care unit (ICU) and discharged within few days. We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support. This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated inflammatory markers, such as serum ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19. The early identification of inflammatory markers should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality − the cytokine storm. This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality. In addition, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19.
托珠单抗治疗合并合并症的重症COVID病态肥胖患者
COVID-19是由新型严重急性呼吸道冠状病毒2引起的,于2019年在中国武汉出现,并导致了当前的大流行。这种疾病继续给治疗带来重大挑战。患者死亡的最终原因是急性呼吸窘迫综合征(ARDS)。由于已知白细胞介素-6 (IL-6)在炎症中起关键作用,IL-6受体抑制剂如托珠单抗可能通过减少细胞因子释放来治疗COVID-19。Tocilizumab是一种重组人源化单克隆抗体,可作为IL-6受体抑制剂。Tocilizumab对炎症和自身免疫性疾病以及类风湿关节炎、巨细胞动脉炎和系统性青少年特发性关节炎的治疗有益。它也被用于治疗COVID-19重症患者。中度至重度疾病患者,需氧量逐渐增加,对皮质类固醇反应不足,炎症标志物水平升高(MoHFW, 2020年6月)。剂量为8mg /kg,在100ml NS中注射60分钟(最大剂量为800mg /次)。如果需要,可在12 - 24小时后重复一次。应仔细监测继发性感染和中性粒细胞减少。HIV、活动性感染、肺结核、活动性肝炎、ANC <2000/mm3、血小板计数<100,000/mm3者禁用。我们报告了我们机构的第一例使用托珠单抗的病例,这是一名57岁的女性,患有中重度COVID-19,即将达到插管要求,需要渐进式氧气支持治疗呼吸窘迫。患者接受托珠单抗治疗以防止细胞因子风暴。我们选择早期给予IL-6抑制剂,因为炎症标志物水平逐渐升高,呼吸状况恶化。该治疗与COVID-19的标准药物治疗(羟氯喹、他扎尔和锌)联合使用耐受性良好。随后,患者在接下来的几天里呼吸系统症状和总体临床状况明显改善。我们认为tocilizumab在她克服临床衰退的能力中发挥了重要作用,特别是需要机械通气。最终,患者从重症监护病房(ICU)转移并在几天内出院。我们强调IL-6抑制剂预防呼吸系统疾病进展到需要呼吸机支持的程度的潜力。该病例强调了早期连续测量IL-6和细胞因子风暴相关炎症标志物(如血清铁蛋白、d -二聚体和c反应蛋白)在指导临床决策和疑似COVID-19患者管理方面的潜在重要性。在COVID-19的治疗中应实施炎症标志物的早期识别,以筛查导致死亡的主要因素-细胞因子风暴。这种筛查,如果在细胞因子风暴的早期积极治疗之后,可能会有最佳的治疗效果,并避免机械通气的需要,从而降低死亡率。此外,我们回顾了目前关于COVID-19中细胞因子释放综合征的证据和使用IL-6受体抑制作为治疗策略,并检查了文献中描述IL-6拮抗剂治疗COVID-19患者的其他报道病例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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